β-Methylnorleucine
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| Category | Antibiotics |
| Catalog number | BBF-01929 |
| CAS | |
| Molecular Weight | 145.20 |
| Molecular Formula | C7H15NO2 |
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Description
β-Methylnorleucine is an amino acid antibiotic produced by Serratia rnarcescens Ar 130-1.
Specification
| Synonyms | beta-Methylnorleucine |
| IUPAC Name | (2S,3R)-2-amino-3-methylhexanoic acid |
| Canonical SMILES | CCCC(C)C(C(=O)O)N |
| InChI | InChI=1S/C7H15NO2/c1-3-4-5(2)6(8)7(9)10/h5-6H,3-4,8H2,1-2H3,(H,9,10)/t5-,6+/m1/s1 |
| InChI Key | KWSUGULOZFMUDH-RITPCOANSA-N |
Properties
| Appearance | Colorless Crystal |
| Boiling Point | 243.4±23.0°C at 760 mmHg |
| Melting Point | 268°C (dec.) |
| Density | 1.0±0.1 g/cm3 |
Reference Reading
1. Glucose-Limited Fed-Batch Cultivation Strategy to Mimic Large-Scale Effects in Escherichia coli Linked to Accumulation of Non-Canonical Branched-Chain Amino Acids by Combination of Pyruvate Pulses and Dissolved Oxygen Limitation
Ángel Córcoles García, Peter Hauptmann, Peter Neubauer Microorganisms. 2021 May 21;9(6):1110. doi: 10.3390/microorganisms9061110.
Insufficient mixing in large-scale bioreactors provokes gradient zones of substrate, dissolved oxygen (DO), pH, and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and β-methylnorleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids (ncBCAA), but also that pyruvate pulses produce the same effect. Therefore, we combined the enzyme-based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor (STR). To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.
2. Natural 2-Amino-3-Methylhexanoic Acid as Plant Elicitor Inducing Resistance against Temperature Stress and Pathogen Attack
He Wang, Jingjing Li, Qian Yang, Lan Wang, Jing Wang, Yaxin Zhang, Yanjing Guo, Rui Li, Ruiqi Zhang, Xiaorong Tao, Bernal E Valverde, Sheng Qiang, Hazem M Kalaji, Shiguo Chen Int J Mol Sci. 2022 May 20;23(10):5715. doi: 10.3390/ijms23105715.
2-Amino-3-methylhexanoic acid (AMHA) was synthetized as a non-natural amino acid more than 70 years ago; however, its possible function as an inducer of plant resistance has not been reported. Plant resistance inducers, also known as plant elicitors, are becoming a novel and important development direction in crop protection and pest management. We found that free AMHA accumulated in the mycelia but not in fermentation broths of four fungal species, Magnaporthe oryzae and three Alternaria spp. We unequivocally confirmed that AMHA is a naturally occurring endogenous (2S, 3S)-α-amino acid, based on isolation, purification and structural analyses. Further experiments demonstrated that AMHA has potent activity-enhancing resistance against extreme temperature stresses in several plant species. It is also highly active against fungal, bacterial and viral diseases by inducing plant resistance. AMHA pretreatment strongly protected wheat against powdery mildew, Arabidopsis against Pseudomonas syringae DC3000 and tobacco against Tomato spotted wilt virus. AMHA exhibits a great potential to become a unique natural elicitor protecting plants against biotic and abiotic stresses.
3. Molecular genetic approaches to decrease the uncontrolled misincorporation of non-canonical branched chain amino acids into recombinant mini-proinsulin expressed in Escherichia coli
Ángel Córcoles García, Peter Hauptmann, Peter Neubauer Microb Cell Fact. 2022 Mar 4;21(1):30. doi: 10.1186/s12934-022-01756-x.
The uncontrolled incorporation of non-canonical branched chain amino acids (ncBCAAs) such as norleucine, norvaline and β-methylnorleucine into recombinant proteins in E. coli production processes is a crucial problem in the pharmaceutical industry, since it can lead to the production of altered proteins with non-optimal characteristics. Despite various solutions, to date there are no engineered strains that exhibit a reduced accumulation of these ncBAAs. In this study, novel E. coli K-12 BW25113 strains with exogenous tunable expression of target genes of the BCAA biosynthetic pathway were developed. For this purpose, single gene knock-outs for thrA, ilvA, leuA, ilvIH, ilvBN, ilvGM and ilvC were complemented with plasmids containing the respective genes under control of an arabinose promoter. These clones were screened in a mL-bioreactor system in fed-batch mode under both standard cultivation conditions and with pyruvate pulses, and induction of a min-proinsulin. Screening was performed by comparing the impurity profile of the recombinant mini-proinsulin expressed of each clone with the E. coli BW25113 WT strain, and the most promising clones were cultivated in a 15L Screening showed that up-regulation of ilvC, ilvIH and ilvGM, and downregulation of leuA and ilvBN trigger a reduction of norvaline and norleucine accumulation and misincorporation into mini-proinsulin. The stirred tank bioreactor cultivations confirmed that up-regulation of ilvIH and ilvGM were most effective to reduce the ncBCAA misincorporation. This novel approach for a reduced ncBCAA misincorporation may be solution to this old challenging problem in the large-scale production of human therapeutics.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
